New Eye Disease: Light BlindnessWhen a photon of light hits a rod or cone photoreceptor cell, it begins the phototransduction cascade that ultimately results in a visual signal sent to the brain. But what happens if the cascade can’t quickly reverse itself?

A collaboration of ophthalmologists and scientists at the Massachusetts Eye and Ear Infirmary and Dutch scientists at the University of Groningen has answered that question—and identified a retinal problem they believe is overlooked in ophthalmologists’ offices. They have named the new disease bradyopsia.

What they found was a small number of patients whose visual acuity can measure 20/20, but whose ability for functional vision is limited because phototransduction fails to turn off properly, the group reported in Nature.1

These patients—quite literally—are blinded by the light when they move from indoors to a sunlit street, or vice versa, said coauthor Thaddeus P. Dryja, MD, surgeon in ophthalmology at MEEI and professor of ophthalmology at Harvard Medical School. “For five to 10 seconds they are blind. They have to stop cold,” Dr. Dryja said. “You and I might squint our eyes in this situation, but we can still walk. These people have to stop altogether. They can’t see a thing. And while they later can see in the bright light, they have trouble the whole time. It never becomes comfortable.”

The patients’ slow visual responses are especially symptomatic when they try to view low-contrast objects in motion. For example, they can’t see 2-inch gray letters slowly going across a computer screen or a baseball traveling across the sky, he said. Some of them have trouble playing ball games.

The reason is a genetic lack of either a protein that turns off phototransduction, RGS9, or the protein substrate to which RGS9 binds, the researchers found.

Dr. Dryja noted that a fellow in his lab, Koji M. Nishiguchi, MD, began looking for affected patients after another group created transgenic mice with RGS9 mutations and visual problems but no retinal degeneration. Electroretinograms showed the mice’s photoreceptors’ deactivated extremely slowly.

“He’s the one who deserves much of the credit for tracking down the phenotype,” Dr. Dryja said. “He looked up every paper in the medical literature since 1980 that had anything to do with ERGs, and finally in a highly specialized ophthalmic electrophysiology journal he found that in 1991 a group from Holland had reported patients with abnormal ERGs like those in the mice.”

Genetic analysis of them, as well as of a Guatemalan patient whom MEEI clinicians recalled from years ago, identified the faulty genes. Dr. Dryja noted that some of the patients had been sent to psychiatrists because their complaints weren’t backed up by Snellen testing.

“I expect there are up to 1,000 people in America who have this condition and whose symptoms are not even seriously considered by their ophthalmologists,” he said. If you find one of them, Dr. Dryja would like to know about it.

Legal UpdateAREDS Vitamins in CourtIf Bausch & Lomb has its way in court, it will hold the exclusive rights for 20 years—until March 23, 2021—to manufacture an eye vitamin developed from a government study. The company filed patent infringement suits in U. S. District Court in Rochester, N.Y., last December against four companies that manufacture or distribute vitamins containing the Age Related Eye Disease Study (AREDS) formula.

The suit seeks to protect the company’s patent rights and “significant investment in ocular nutritional research and development.” That investment was in the “tens of millions of dollars,” said Margaret Graham, a company spokeswoman, who would not disclose the exact amount.

And the NIH, under whose auspices the NEI conducted AREDS, will not say how much money it expects to receive in royalties from Bausch & Lomb. That money will be “plowed back into research,” the kind, presumably, that led to the AREDS finding that megadoses of antioxidants and minerals could retard the progression of macular degeneration in patients with moderate to advanced cases of the blinding disease.

Much is riding on the outcome of this lawsuit. When AREDS was conceived, more than a decade ago, 15 percent of the population, or 10 million persons, were estimated to be taking high-dose antioxidants.

A law, known as the Cooperative Research and Development Agreement, or CRADA, allows such private-public collaboration, “where we have a mutual interest and complementary capabilities . . . to facilitate the development of new technologies that ultimately lead to new products,” said Mark Rohrbaugh, PhD, JD, director of the Office of Technology Transfer at NIH. CRADA requires the NIH to offer the commercial partner the option to take an exclusive license to new inventions.

At the time that the NEI was looking for a partner to develop the vitamins used in the study, there were few takers, Dr. Rohrbaugh added. “The NEI did an extensive search for partners. Of the few that were interested, only one had the capability to provide what was needed.” That company was the Storz division of American Cyanamid, which was sold to Bausch & Lomb in December 1997.

The four defendants are Alcon, General Nutrition Companies, Leiner Health Products and Rexall Sundown, though other companies also manufacture AREDS-style vitamins. Some modify the formula, by adding lutein, for example. The courts will have to decide whether that constitutes a patent infringement, said Ms. Graham. “I do know that our patent rights are very broad.”

—Miriam Karmel

Research ReportWhen Ears Help People SeeWhen a myope can’t find his eyeglasses first thing in the morning, that might actually be a blessing in disguise, suggest recent studies by researchers in North Carolina.

That’s because what in the past might have seemed like an old wives’ tale turns out to be true: impaired vision heightens the brain’s ability to use other senses to navigate, said Mark Wallace, PhD, an associate professor of neurobiology and anatomy at Wake Forest University Baptist Medical Center in Winston-Salem.

“One of the holy grails of the study of multisensory integration has been to try to show that the combination of vision and audition helps us locate things in space,” Dr. Wallace said. “But no one had been able to show it. We were able to unmask a multisensory effect by isolating the two senses from each other.”

He and colleagues compared the performance of emmetropic subjects before and after they wore goggles that produced 6D of myopia. In a darkened room, the task was to point to a randomly placed flash of light—which was sometimes accompanied by a sound.

The data showed that emmetropic vision is so good that location-indicating sounds are redundant. But, when the subjects were made myopic and couldn’t locate the light as well visually, the addition of sound improved their performance markedly, Dr. Wallace said. “Suddenly their performance improved, and in fact they were as good as they were with 20/20 vision,” he said.

The study confirms the benefits of teaching low vision patients how to use their other senses to make up for visual loss, Dr. Wallace said.

Retinoblastoma ReportEugenics and the EyePrenatal diagnosis has become routine in families with hereditary diseases such as retinoblastoma—but deciding whether to terminate a pregnancy based on the diagnosis remains an emotionally wrenching process for prospective parents.

So it was with pride earlier this year that physicians at Weill Cornell School of Medicine in New York City announced that, for the first time, preimplantation genetic diagnosis (PGD) had been used to produce a healthy, RB-free baby.

A paper in the January American Journal of Ophthalmology1 detailed the process leading to the couple’s RB-free child, now 2 years old. The parents had a second unaffected baby using in vitro fertilization (IVF) with PGD while the researchers were making sure everything went well before publishing the results on the first, said David H. Abramson, MD, a coauthor who recently became chief of ophthalmic oncology at Memorial Sloan Kettering Cancer Center.

The team’s jubilation was especially high because so much can, and did, get in the way of success, Dr. Abramson said. “We’ve had other families where for one or more reasons we couldn’t continue with the entire technique,” he said.

“All the stars have to be right to be successful here. It’s a multifaceted puzzle, and if one facet doesn’t fit the whole thing doesn’t work.”

First, it has to be possible to identify the specific mutation causing RB in the affected parent, which can be done only 85 percent of the time, he said. Then a molecular biologist has to be able to build a probe to detect it in the embryo. Last, the in vitro fertilization and implantation must succeed, followed by a normal pregnancy.

Still, the proof-of-principle means that any institution with a strong in vitro fertilization program should be able to offer PGD to couples with genes for retinoblastoma or, perhaps, other congenital blinding diseases, Dr. Abramson said.

Business ReportPhaco Patent Suit Reveals Competitive MarketTwo of the top three manufacturers of cataract surgery equipment are embroiled in a legal battle that shows just how competitive the more than $200 million U. S. cataract device market has become.

Citing a responsibility to its shareholders and customers, Advanced Medical Optics (AMO) filed a patent infringement suit last December against Alcon, which leads the pack in the U.S. cataract surgical equipment market. The suit attempts to stop Alcon from selling two of its phacoemulsification machines: the Infiniti Vision system and the Series 20000 Legacy.

The suit asserts that certain design features in the Alcon machines copy those found in AMO’s Sovereign and Sovereign Compact phacoemulsification systems.

“This infringement looks so much like our technology that it was just something we had to address,” Russ Trenary, corporate vice president of AMO said.

Two patents are cited in the suit. One, issued Dec. 23, 1997, enables the phacoemulsification system to shift power when the tip of a hand piece encounters a piece of the cataract that occludes the tip.

The second, issued May 9, 2000, covers the method for ensuring that air is adequately purged from the vacuum sensor, thus creating a more stable operating environment.

AMO is seeking monetary damages and a permanent injunction against future sales of the Alcon machines. “We’ve made significant investments in the development of these technologies and these are key to our competitive position in the marketplace,” Mr. Trenary said.

Alcon denies any wrongdoing. “Whether the products look alike means nothing,” said Kathleen Knight, a company vice president and deputy general counsel. “They have to prove that Alcon’s product contains every element of the claim of the patent.”

“I was surprised [by the suit] because both patents had been in existence, and they had not previously asserted them against us,” she said.